14,832 research outputs found

    Fusion of twisted representations

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    The comultiplication formula for fusion products of untwisted representations of the chiral algebra is generalised to include arbitrary twisted representations. We show that the formulae define a tensor product with suitable properties, and determine the analogue of Zhu's algebra for arbitrary twisted representations. As an example we study the fusion of representations of the Ramond sector of the N=1 and N=2 superconformal algebra. In the latter case, certain subtleties arise which we describe in detail.Comment: 24 pages, LATE

    A Systems Biology Approach towards Deciphering the Unfolded Protein Response in Huntington's Disease

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    Although the disease causing gene huntingtin has been known for some time, the exact cause of neuronal cell death during _Huntington's disease_ (HD) remains unknown. One potential mechanism contributing to the massive loss of neurons in HD brains might be the _Unfolded Protein Response_ (UPR) which is activated by accumulation of misfolded proteins in the endoplasmic reticulum (ER). As an adaptive response, UPR upregulates transcription of chaperones, temporarily attenuating new translation and activates protein degradation via the proteasome. However, at high levels of ER stress, UPR signalling can contribute to neuronal apoptosis.

Our primary aims include (a) construction of the UPR signalling network, (b) curation and bioinformatical identification of UPR target genes and finally (c) examination of HD gene expression data sets for UPR transcriptional signatures and differential regulation of UPR pathways.

The UPR signalling pathway is reconstructed based on literature review and using the "Unified Interactome database":http://www.unihi.org. Lists of UPR target genes detected by previous experiments or as predicted by computational analysis are compiled. This allows us to perform enrichment analysis for differential HD gene expression and to assess whether UPR expression signatures are prominent during HD pathogenesis.

Results: The canonical UPR pathway is complemented with additional protein interaction data allowing us to assess its embedding into the cellular context and to identify potential modifiers as well as novel drug targets.

Conclusions: The in depth systems biology analysis can give us valuable insights about the involvement of the UPR in HD.
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    The Unfolded Protein Response and its potential role in Huntington's disease

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    Huntington's disease (HD) is a progressive, neurodegenerative disease with fatal outcome. Although the disease-causing gene (huntingtin) has been known for some time, the exact cause of neuronal cell death is still unknown. One potential mechanism contributing to the massive loss of neurons in the brain of HD patients might be the unfolded protein response (UPR), which is activated by accumulation of misfolded proteins in the endoplasmatic reticulum (ER). As an adaptive response to counter-balance accumulation of un- or misfolded proteins, the UPR upregulates transcription of chaperones, temporarily attenuates new translation, and activates protein degradation via the proteasome. However, it is known that persistent ER stress and activated UPR can cause cell death by triggering of apoptosis. Nevertheless, the evidence linking UPR with HD progression remains inconclusive. Here, we present first analyses of UPR activation during HD based on available expression data. To elucidate the potential role of UPR as a disease-relevant process, we examine its connection to cell death and inflammatory processes. Due to the complexity of these molecular mechanisms, a systems biology approach was pursued

    Intonation in unaccompanied singing: Accuracy, drift, and a model of reference pitch memory

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    Copyright 2014 Acoustical Society of America. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the Acoustical Society of America. The following article appeared in J. Acoust. Soc. Am. 136, 401 (2014) and may be found at http://dx.doi.org/10.1121/1.4881915

    The Incidence and Clinical Relevance of Graft Hypertrophy After Matrix-Based Autologous Chondrocyte Implantation

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    Background: Graft hypertrophy is the most common complication of periosteal autologous chondrocyte implantation (p-ACI). Purpose: The aim of this prospective study was to analyze the development, the incidence rate, and the persistence of graft hypertrophy after matrix-based autologous chondrocyte implantation (mb-ACI) in the knee joint within a 2-year postoperative course. Study Design: Case series; Level of evidence, 4. Methods: Between 2004 and 2007, a total of 41 patients with 44 isolated cartilage defects of the knee were treated with the mb-ACI technique. The mean age of the patients was 35.8 years (standard deviation [SD], 11.3 years), and the mean body mass index was 25.9 (SD, 4.2; range, 19-35.3). The cartilage defects were arthroscopically classified as Outerbridge grades III and IV. The mean area of the cartilage defect measured 6.14 cm2 (SD, 2.3 cm2). Postoperative clinical and magnetic resonance imaging (MRI) examinations were conducted at 3, 6, 12, and 24 months to analyze the incidence and course of the graft. Results: Graft hypertrophy developed in 25% of the patients treated with mb-ACI within a postoperative course of 1 year; 16% of the patients developed hypertrophy grade 2, and 9% developed hypertrophy grade 1. Graft hypertrophy occurred primarily in the first 12 months and regressed in most cases within 2 years. The International Knee Documentation Committee (IKDC) and visual analog scale (VAS) scores improved during the postoperative follow-up time of 2 years. There was no difference between the clinical results regarding the IKDC and VAS pain scores and the presence of graft hypertrophy. Conclusion: The mb-ACI technique does not lead to graft hypertrophy requiring treatment as opposed to classic p-ACI. The frequency of occurrence of graft hypertrophy after p-ACI and mb-ACI is comparable. Graft hypertrophy can be considered as a temporary excessive growth of regenerative cartilage tissue rather than a true graft hypertrophy. It is therefore usually not a persistent or systematic complication in the treatment of circumscribed cartilage defects with mb-ACI

    Nonequilibrium Magnetization Dynamics of Nickel

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    Ultrafast magnetization dynamics of nickel has been studied for different degrees of electronic excitation, using pump-probe second-harmonic generation with 150 fs/800 nm laser pulses of various fluences. Information about the electronic and magnetic response to laser irradiation is obtained from sums and differences of the SHG intensity for opposite magnetization directions. The classical M(T)-curve can be reproduced for delay times larger than the electron thermalization time of about 280 fs, even when electrons and lattice have not reached thermal equilibrium. Further we show that the transient magnetization reaches its minimum approx. 50 fs before electron thermalization is completed.Comment: 8 pages, 5 figures, revte

    Numerical Renormalization Group for Impurity Quantum Phase Transitions: Structure of Critical Fixed Points

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    The numerical renormalization group method is used to investigate zero temperature phase transitions in quantum impurity systems, in particular in the particle-hole symmetric soft-gap Anderson model. The model displays two stable phases whose fixed points can be built up of non-interacting single-particle states. In contrast, the quantum phase transitions turn out to be described by interacting fixed points, and their excitations cannot be described in terms of free particles. We show that the structure of the many-body spectrum of these critical fixed points can be understood using renormalized perturbation theory close to certain values of the bath exponents which play the role of critical dimensions. Contact is made with perturbative renormalization group calculations for the soft-gap Anderson and Kondo models. A complete description of the quantum critical many-particle spectra is achieved using suitable marginal operators; technically this can be understood as epsilon-expansion for full many-body spectra.Comment: 14 pages, 12 figure

    Three-dimensional shear in granular flow

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    The evolution of granular shear flow is investigated as a function of height in a split-bottom Couette cell. Using particle tracking, magnetic-resonance imaging, and large-scale simulations we find a transition in the nature of the shear as a characteristic height HH^* is exceeded. Below HH^* there is a central stationary core; above HH^* we observe the onset of additional axial shear associated with torsional failure. Radial and axial shear profiles are qualitatively different: the radial extent is wide and increases with height while the axial width remains narrow and fixed.Comment: 4 pages, 5 figure

    The Nature of Transition Circumstellar Disks II. Southern Molecular Clouds

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    Transition disk objects are pre-main-sequence stars with little or no near-IR excess and significant far-IR excess, implying inner opacity holes in their disks. Here we present a multifrequency study of transition disk candidates located in Lupus I, III, IV, V, VI, Corona Australis, and Scorpius. Complementing the information provided by Spitzer with adaptive optics (AO) imaging (NaCo, VLT), submillimeter photometry (APEX), and echelle spectroscopy (Magellan, Du Pont Telescopes), we estimate the multiplicity, disk mass, and accretion rate for each object in our sample in order to identify the mechanism potentially responsible for its inner hole. We find that our transition disks show a rich diversity in their spectral energy distribution morphology, have disk masses ranging from lsim1 to 10 M JUP, and accretion rates ranging from lsim10-11 to 10-7.7 M \odot yr-1. Of the 17 bona fide transition disks in our sample, three, nine, three, and two objects are consistent with giant planet formation, grain growth, photoevaporation, and debris disks, respectively. Two disks could be circumbinary, which offers tidal truncation as an alternative origin of the inner hole. We find the same heterogeneity of the transition disk population in Lupus III, IV, and Corona Australis as in our previous analysis of transition disks in Ophiuchus while all transition disk candidates selected in Lupus V, VI turned out to be contaminating background asymptotic giant branch stars. All transition disks classified as photoevaporating disks have small disk masses, which indicates that photoevaporation must be less efficient than predicted by most recent models. The three systems that are excellent candidates for harboring giant planets potentially represent invaluable laboratories to study planet formation with the Atacama Large Millimeter/Submillimeter Array.Comment: 62 pages, 13 figure
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